LPS-INDUCED INCREASE OF THYROGLOBULIN (TG) GENE EXPRESSION INVOLVES TTF-1 AND PAX-8 TRANSCRIPTION FACTORS IN RAT THYROID CELLS.

VÉLEZ MARIA LAURA; FOZZATTI LAURA; MONTESINOS MARIA DEL MAR; LUCERO ARIEL MAXIMILIANO; MASINI-REPISO ANA MARIA

Iguazú, Misiones.

Congreso; Congreso de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB).; 2004

Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB).

Bacterial lipopolysaccharide (LPS) induces multiple gene expression in several cell types. LPS action on thyroid function has not been studied. We previously demonstrated an LPS-induced stimulation of iodide uptake and iodide transporter expression in rat thyroid cell line FRTL-5. Here we analyse the LPS effect on TG gene expression. An increase of TG level was observed after 24-48h of LPS treatment. LPS induced an increase in TG mRNA after 3-6h which was reduced at 48h. In cells transfected with minimal TG promoter containing thyroid transcription factor-1 (TTF-1), TTF-2 and Pax-8/TTF-1 (C-site) binding sites, LPS increased transcriptional activity at 18-24h and decreased it at 48h. A lack of response to LPS was observed transfecting a Pax-8-site mutated promoter. LPS activated transcription of a construct with 5 C-sites. The binding of TTF-1 and Pax-8 to a C-site oligonucleotide was increased by LPS (EMSA). LPS increased TTF-1 and Pax-8 mRNA (3h) and protein (12h) expression. These results indicate that the LPS-induced increase of TG involves transcriptional activation of TG gene by mediation, at least in part, of TTF-1 and Pax-8. An increase of transcription factors binding to the TG promoter and the induction of TTF-1 and Pax-8 expression could be involved. In conclusion, these findings revealed that LPS is able to stimulate TG gene expression, a fact of possible pathophysiological significance.